| First Author | Mukherjee S | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 1 | Pages | 248-58 |
| PubMed ID | 21703407 | Mgi Jnum | J:174003 |
| Mgi Id | MGI:5050769 | Doi | 10.1016/j.ajpath.2011.03.003 |
| Citation | Mukherjee S, et al. (2011) IL-17-Induced Pulmonary Pathogenesis during Respiratory Viral Infection and Exacerbation of Allergic Disease. Am J Pathol 179(1):248-58 |
| abstractText | Severe respiratory syncytial virus (RSV) infections are characterized by airway epithelial cell damage, mucus hypersecretion, and Th2 cytokine production. Less is known about the role of IL-17. We observed increased IL-6 and IL-17 levels in tracheal aspirate samples from severely ill infants with RSV infection. In a mouse model of RSV infection, time-dependent increases in pulmonary IL-6, IL-23, and IL-17 expression were observed. Neutralization of IL-17 during infection and observations from IL-17(-/-) knockout mice resulted in significant inhibition of mucus production during RSV infection. RSV-infected animals treated with anti-IL-17 had reduced inflammation and decreased viral load, compared with control antibody-treated mice. Blocking IL-17 during infection resulted in significantly increased RSV-specific CD8 T cells. Factors associated with CD8 cytotoxic T lymphocytes, T-bet, IFN-gamma, eomesodermin, and granzyme B were significantly up-regulated after IL-17 blockade. Additionally, in vitro analyses suggest that IL-17 directly inhibits T-bet, eomesodermin, and IFN-gamma in CD8 T cells. The role of IL-17 was also investigated in RSV-induced exacerbation of allergic airway responses, in which neutralization of IL-17 led to a significant decrease in the exacerbated disease, including reduced mucus production and Th2 cytokines, with decreased viral proteins. Taken together, our data demonstrate that IL-17 plays a pathogenic role during RSV infections. |
